NIMH and Johns Hopkins University are investigating the changes in receptor numbers in response to the loss of neuronal input in experimental animals as a potential explanation for previously reported aberrations in cerebrospinal fluid and brains of patients with the schizophrenic syndrome. Utilizing tritium labeled ligands, the technique of in vitro autoradiography and computerized densitometry have been used to assess the changes in receptor numbers resulting from denervation in animals with subsequent reversal following successful transplantation of replacement tissue in a rat model for denervation supersensitivity. In humans, preliminary evidence suggests that norepinephrine containing cell bodies at the locus coeruleus have fewer binding sites for NE feedback inhibition than comparable normals and suicide victims. This later finding is in keeping with previous reports of increased NE in brain regions post-mortem of schizophrenic patients. The nature of this finding, whether it be a neuroleptic effect or an important clue to the pathophysiology of at least a subtype of the schizophrenic syndrome has yet to be determined.